PY 108-068, a dihydropyridine derivative, and verapamil interact differently with the ouabain effects on the heart and the peripheral circulation

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Abstract
In previous experiments PY 108-068 (PY) has been found to have more potent calcium antagonistic effects on vascular smooth muscle than on myocardial tissue. We now investigated the effects of PY and verapamil (V) on the increases in myocardial contractile force (measured with a strain gauge) and regional vasoconstriction (measured with tracer microspheres) effected by an infusion of 40 μg/kg ouabain into anaesthetized cats. Ouabain significantly increased contractile force of the left ventricle and caused vasoconstriction in the heart, stomach, small intestine, pancreas, spleen and skin, but not in the kidneys, brain, adrenals and liver. PY (30 μg/kg i.v.) and V (0.3 mg/kg i.v.) antagonized the vasoconstrictor effects of the glycoside in all organs except the skin, i.e. also in organs, where the calcium antagonists normally do not cause vasodilatation. However, PY did not affect the increase in contractile force, whereas V attenuated both the cardiac and peripheral vascular effects of ouabain. The results demonstrate the preferential action of PY on peripheral blood vessels as opposed to left ventricular myocardial tissue. Heart rate was decreased by both PY and V but the PQ-interval was lengthened only by V suggesting that PY in contrast to V preferentially acts on the sinus node rather than A-V conduction. A combination of PY with a glycoside might be beneficial in the treatment of cardiac failure, since this calcium antagonist apparently does not antagonize the positive inotropic action of ouabain on the heart while reducing afterload and reversing the undesirable vasoconstriction induced by cardiac glycosides.